Over the next few years, my laboratory will carry out investigations of cell surface proteins, their role in growth control, and the way in which these are altered during viral transformation. We shall employ external labelling procedures such as lactoperoxidase- catalyzed iodination. These methods allow one to study specifically those proteins which are exposed at the outer cell surface. Use will also be made of viruses temperature sensitive for maintenance of the transformed state. In this way we shall investigate alterations in these proteins during regulation of growth in normal cells and on transformation by oncogenic viruses. External labelling techniques will assist in purifying the molecules of interest and antibodies will be prepared. These reagents will then be used to test hypotheses about the role of surface proteins in growth regulation. In particular, we shall investigate the properties of a large external glycoprotein which our earlier work has shown to be sensitive to transformation and proteolysis and to be regulated in normal fibroblasts. Synthesis and metabolism will be studied as will be the manner in which these are altered by transformation. We shall also investigate the possible role of proteases in producing alterations in cell surface proteins during transformation. The objective of this research will be to gain better understanding of the mechanisms by which events at the cell surface affect the internal functions of the cell, and vice versa.